Variation in germline mtDNA heteroplasmy is determined prenatally but modified during subsequent transmission

Nature Genetics

Volumn 44, Issue 11, 2012, Pages 1282-1285

  Freyer, Christoph ^a,b   Cree, Lynsey M ^c   Mourier, Arnaud ^a   Stewart, James B ^a   Koolmeister, Camilla ^b   Milenkovic, Dusanka ^a   Wai, Timothy ^d   Floros, Vasileios I ^c   Hagström, Erik ^b   Chatzidaki, Emmanouella E ^b   Wiesner, Rudolf J ^d   Samuels, David C ^e   Larsson, Nils Göran ^a,b   Chinnery, Patrick F ^c  

^a MAX PLANCK INSTITUTE FOR BIOLOGY OF AGEING   (Germany)

^b KAROLINSKA INSTITUTE   (Sweden)

^c NEWCASTLE UNIVERSITY   (United Kingdom)

^d UNIVERSITY OF COLOGNE   (Germany)

^e VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MITOCHONDRIAL DNA; MITOCHONDRIAL RNA; TRANSFER RNA;

AMINOACYLATION; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; FEMALE; FERTILITY; GENE DELETION; GENE MUTATION; GENETIC COUNSELING; GENETIC DRIFT; GERM CELL; HETEROPLASMY; MAMMAL; MITOCHONDRIAL DNA DISORDER; MITOCHONDRIAL ENCEPHALOMYOPATHY; MITOCHONDRIAL GENOME; MITOCHONDRIAL RESPIRATION; MOUSE; NEWBORN; NONHUMAN; OOCYTE; OOCYTE DEVELOPMENT; PHENOTYPE; PRIORITY JOURNAL; PROGENY; PURIFYING SELECTION; RESPIRATORY CHAIN; TRANSCRIPTION INITIATION;

ANIMALS; DNA, MITOCHONDRIAL; DNA-DIRECTED DNA POLYMERASE; FEMALE; FERTILITY; GENETIC HETEROGENEITY; GENOME, MITOCHONDRIAL; GERM-LINE MUTATION; MICE; MICE, INBRED C57BL; OOCYTES; RNA; RNA, TRANSFER, MET;

MAMMALIA; MUS;

EID: 84868211657     PISSN: 10614036     EISSN: 15461718     Source Type: Journal    
DOI: 10.1038/ng.2427     Document Type: Article

References (23)

1. Upholt, W.B. & Dawid, I.B. Mapping of mitochondrial DNA of individual sheep and goats: rapid evolution in the D loop region. Cell 11, 571-583 (1977).
2. Olivo, P.D., Van de Walle, M.J., Laipis, P.J. & Hauswirth, W.W. Nucleotide sequence evidence for rapid genotypic shifts in the bovine mitochondrial DNA D-loop. Nature 306, 400-402 (1983).
3. Cao, L. et al. The mitochondrial bottleneck occurs without reduction of mtDNA content in female mouse germ cells. Nat. Genet. 39, 386-390 (2007).
4. Cree, L.M. et al. A reduction of mitochondrial DNA molecules during embryogenesis explains the rapid segregation of genotypes. Nat. Genet. 40, 249-254 (2008).
5. Wai, T., Teoli, D. & Shoubridge, E.A. The mitochondrial DNA genetic bottleneck results from replication of a subpopulation of genomes. Nat. Genet. 40, 1484-1488 (2008).
6. Wonnapinij, P., Chinnery, P.F. & Samuels, D.C. Previous estimates of mitochondrial DNA mutation level variance did not account for sampling error: comparing the mtDNA genetic bottleneck in mice and humans. Am. J. Hum. Genet. 86, 540-550 (2010).
7. Samuels, D.C., Wonnapinij, P., Cree, L.M. & Chinnery, P.F. Reassessing evidence for a postnatal mitochondrial genetic bottleneck. Nat. Genet. 42, 471-472 (2010).
8. Chinnery, P.F. et al. The inheritance of mitochondrial DNA heteroplasmy: random drift, selection or both? Trends Genet. 16, 500-505 (2000).
9. Uusimaa, J. et al. Prevalence, segregation, and phenotype of the mitochondrial DNA 3243AG mutation in children. Ann. Neurol. 62, 278-287 (2007).
10. Trifunovic, A. et al. Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature 429, 417-423 (2004).
11. Stewart, J.B. et al. Strong purifying selection in transmission of mammalian mitochondrial DNA. PLoS Biol. 6, e10 (2008).
12. Stewart, J.B., Freyer, C., Elson, J.L. & Larsson, N.G. Purifying selection of mtDNA and its implications for understanding evolution and mitochondrial disease. Nat. Rev. Genet. 9, 657-662 (2008).
13. Manfredi, G. et al. Identification of a mutation in the mitochondrial tRNACys gene associated with mitochondrial encephalopathy. Hum. Mutat. 7, 158-163 (1996).
14. Santorelli, F.M. et al. Mitochondrial tRNACys gene mutation (A5814G): a second family with mitochondrial encephalopathy. Neuromuscul. Disord. 7, 156-159 (1997).
15. Wonnapinij, P., Chinnery, P.F. & Samuels, D.C. The distribution of mitochondrial DNA heteroplasmy due to random genetic drift. Am. J. Hum. Genet. 83, 582-593 (2008).
16. Payer, B. et al. Generation of stella-GFP transgenic mice: a novel tool to study germ cell development. Genesis 44, 75-83 (2006).
17. Fan, W. et al. A mouse model of mitochondrial disease reveals germline selection against severe mtDNA mutations. Science 319, 958-962 (2008).
18. Metodiev, M.D. et al. Methylation of 12S rRNA is necessary for in vivo stability of the small subunit of the mammalian mitochondrial ribosome. Cell Metab. 9, 386-397 (2009).
19. Cámara, Y. et al. MTERF4 regulates translation by targeting the methyltransferase NSUN4 to the mammalian mitochondrial ribosome. Cell Metab. 13, 527-539 (2011).
20. Boulet, L., Karpati, G. & Shoubridge, E.A. Distribution and threshold expression of the tRNALys mutation in skeletal muscle of patients with myoclonic epilepsy and ragged-red fibers (MERRF). Am. J. Hum. Genet. 51, 1187-1200 (1992).
21. Brown, D.T., Samuels, D.C., Michael, E.M., Turnbull, D.M. & Chinnery, P.F. Random genetic drift determines the level of mutant mitochondrial DNA in human primary oocytes. Am. J. Hum. Genet. 68, 533-536 (2001).
22. Freyer, C. et al. Maintenance of respiratory chain function in mouse hearts with severely impaired mtDNA transcription. Nucleic Acids Res. 38, 6577-6588 (2010).
23. Schägger, H. & von Jagow, G. Blue native electrophoresis for isolation of membrane protein complexes in enzymatically active form. Anal. Biochem. 199, 223-231 (1991).